Receptor-ligand interactions defining

The idea of drug-target residence time places less emphasis on the strength of receptor-ligand interaction and more emphasis on the duration of receptor-ligand interaction. The duration of interaction is defined as the residence time (t) of the ligand, which is equal to the inverse of koff (Equation 5.23). A closely related variable is dissociative half-life (/, 2), also defined by koll (Equation 5.24).31... 

The chemotaxis of mononuclear leukocytes and the migration, growth, and activation of the multiple cell types within atherosclerotic lesions are critical for the chronic inflammatory and fibroproliferative response in atherosclerosis (Ml). Chemokine-mediated attraction of leukocytes to tissues has been shown in atherosclerotic lesions (G8). Studies using knockout and transgenic murine models indicated that chemokine receptor/ligand interactions are crucial in the development of atherosclerosis (P6). Moreover, chemokines may also interfere with smooth muscle cell migration and growth, and platelet activation and other well-defined features of the atherosclerotic process (A2). 

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

Two very similar molecules are two different physical objects [40], Hence, chemical/ structural comparison of similarity is a subtle and relative concept that acquires significance in a well-defined reference physical context. In other words, it is necessary to define in what respect and to what extent two different molecules are similar. Molecular series of specific and selective ligands interacting, in vitro and in equilibrium conditions, with a specific receptor constitute a sophisticated example of chemical similarity-diversity classification. This classification is based on the experimental binding affinity (AG°) values that quantify a particular molecular recognition phenomenon, which is, essentially, a noncovalent process [41]. This implies,... 

As stated before, in the FLAP software the pharmacophores for a ligand are defined in terms of atom types, which can interact with the receptor. The types of interaction are categorized as ... 

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